Glycyrrhetinic Acid (GA), the active principal in liquorice root, has been shown to markedly inhibit 11.beta.-hydroxysteroid dehydrogenase (11.beta.-OHSD) and steroid 5.beta.-reductase when incubated with these enzymes (Stewart, P. M. et al. (1987) Lancet 2:821-823; Monder, C. et al. (1989) Endocrinology 125:1046-1053; Latif, S. A. et al. (1990) Steroids 55:52-58). The importance of both these enzymes has become apparent following the experiments of Ulick, New, Monder and co-workers (Ulick, S. et al. (1979) J. Clin. Endocrin. Metab. 49:747-764; New, M. I. et al. (1982) Endocrinology of Hypertension, Serono Symposium, vol. 50, pp 85-101; Monder, C. et al. (1986) J. Clin. Endocrin. Metab. 63:550-557) who demonstrated that hypertensive children with the syndrome of apparent mineralocorti-coid excess (AME) lack both 11.beta.-OHSD and 5.beta.-reductase activity. Alteration in these enzymatic pathways of steroid inactivation was shown to result in changes in the peripheral metabolism of cortisol. It has been postulated that higher peripheral and intrarenal concentrations of cortisol may then interact with mineralocorticoid receptors and promote sodium reabsorption (Edwards, C. R. W. et al. (1988) Lancet 2:986-989; Funder, J. W. et al. (1988) Science 242:583-585).
AME patients exhibit sodium retention, potassium wasting, and increased blood pressure without measurably increased circulating aldosterone. A pharmacological equivalent of this congenital condition results from the ingestion of liquorice which contains glycoside derivatives of GA (Stewart, P. M. et al. (1987) Lancet 2:821-823; Edwards, C. R. W. et al. (1988) Lancet 2:986-989). Because of the importance of these enzymes, it is possible that other categories of hypertension may also result from less extreme alterations of their activities.